Methods of Treating Skin Disorders with Caffeic Acid Analogs

• US 20100152143A1
• Filed: 09/30/2009
• Published: 06/17/2010
• Est. Priority Date: 09/30/2008
• Status: Active Grant

• Current Assignee: Moleculin, LLC (Moleculin Biotech, Inc.)
• Original Assignee: Moleculin, LLC (Moleculin Biotech, Inc.)
• Inventors: Priebe, Waldemar, Conrad, Charles, Madden, Timothy
• Granted Patent: US 8,450,337 B2
• Time in Patent Office: Days
• US Class Current: 514/167
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/203 Retinoic acids ; Salts thereof
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: C07D 213/61 Halogen atoms or nitro radicals

Abstract

Embodiments of the invention generally relate to pharmaceutical compositions containing at least one caffeic acid compound and methods for the topical treatment of proliferative and inflammatory skin disorders such as plaque psoriasis, atopic dermatitis, and other disorders. In some embodiments, the topical treatment includes applications of the pharmaceutical composition containing at least one caffeic acid compound or a mixture of caffeic acid compounds such as caffeic acid ester compounds, caffeic acid amide compounds, analogues thereof, derivatives thereof, salts thereof, or mixtures thereof. The pharmaceutical composition or topical dosage may contain the caffeic acid compound at a concentration by weight within a range from about 0.01% to about 20%, preferably, from about 0.1% to about 15%, preferably, from about 1% to about 10%, more preferably, from about 3% to about 7%, and more preferably, from about 4% to about 6%.

Claims

1. A method for treating proliferative skin disorders, comprising:

applying a topical pharmaceutical composition to a lesion, wherein the topical pharmaceutical composition comprises a caffeic acid amide compound having the chemical structure of;

where X is a halogen and R is hydrogen, hydroxyl, alkyl, alkoxy, C₃-C₇-cycloalkyl, C₆-C₁₀-aryl, C₇-C₁₀-aralkyl, heteroatom-substituted or heteroatom-unsubstituted, isomers thereof, or derivatives thereof, and the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 0.01% to about 20%.

2. The method of claim 1, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 1% to about 10%.

3. The method of claim 2, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 3% to about 7%.

4. The method of claim 1, wherein the caffeic acid amide compound has the chemical structure of:

5. The method of claim 1, wherein the caffeic acid amide compound has the chemical structure of:

6. The method of claim 1, wherein the caffeic acid amide compound has the chemical structure of:

7. The method of claim 1, wherein the topical pharmaceutical composition further comprises at least one mechanistic compound selected from the group consisting of cell differentiating agents, anti-proliferative agents, mitochondrial inhibitors, topical steroids, immunosuppressive compounds, JAK2 inhibitors, JAK3 inhibitors, parathyroid hormone-related protein (PTHrP) agonists, cell adhesion blockers, derivatives thereof, and combinations thereof.

8. The method of claim 1, wherein the topical pharmaceutical composition further comprises retinoic acid, retinoic acid derivative, vitamin D, or vitamin D analog as a cell differentiating agent.

9. The method of claim 1, wherein the topical pharmaceutical composition is applied multiple times daily until symptoms of the disorder disappear.

10. A method for treating proliferative skin disorders, comprising:

applying a topical pharmaceutical composition to a lesion, wherein the topical pharmaceutical composition comprises a caffeic acid amide compound having the chemical structure of;

and the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 0.01% to about 20%.

11. The method of claim 10, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 1% to about 10%.

12. The method of claim 11, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 3% to about 7%.

13. The method of claim 10, wherein the topical pharmaceutical composition further comprises at least one mechanistic compound selected from the group consisting of cell differentiating agents, anti-proliferative agents, mitochondrial inhibitors, topical steroids, immunosuppressive compounds, JAK2 inhibitors, JAK3 inhibitors, parathyroid hormone-related protein (PTHrP) agonists, cell adhesion blockers, derivatives thereof, and combinations thereof.

14. The method of claim 10, wherein the topical pharmaceutical composition further comprises retinoic acid, retinoic acid derivative, vitamin D, or vitamin D analog as a cell differentiating agent.

15. The method of claim 10, wherein the topical pharmaceutical composition is applied multiple times daily until symptoms of the disorder disappear.

16. A pharmaceutical composition for topical application to psoriatic lesions, comprising:

a carrier suitable for topical administration; and

a caffeic acid amide compound having the chemical structure of;

where X is a halogen and R is hydrogen, hydroxyl, alkyl, alkoxy, C₃-C₇-cycloalkyl, C₆-C₁₀-aryl, C₇-C₁₀-aralkyl, heteroatom-substituted or heteroatom-unsubstituted, isomers thereof, or derivatives thereof, and the caffeic acid amide compound is at a concentration by weight within a range from about 0.01% to about 20% of the pharmaceutical composition.

17. The pharmaceutical composition of claim 16, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 1% to about 10%.

18. The pharmaceutical composition of claim 17, wherein the topical pharmaceutical composition comprises the caffeic acid amide compound at a concentration by weight within a range from about 3% to about 7%.

19. The pharmaceutical composition of claim 16, further comprising petroleum jelly or dimethyl sulfoxide.

20. The pharmaceutical composition of claim 16, further comprising at least one mechanistic compound selected from the group consisting of cell differentiating agents, anti-proliferative agents, mitochondrial inhibitors, topical steroids, immunosuppressive compounds, JAK2 inhibitors, JAK3 inhibitors, parathyroid hormone-related protein (PTHrP) agonists, cell adhesion blockers, derivatives thereof, and combinations thereof.

21. The pharmaceutical composition of claim 16, further comprising a cell differentiating agent selected from at least one of retinoic acid, retinoic acid derivative, vitamin D, or vitamin D analog.

22. The pharmaceutical composition of claim 16, wherein the caffeic acid amide compound has the chemical structure of:

23. The pharmaceutical composition of claim 16, wherein the caffeic acid amide compound has the chemical structure of:

24. The pharmaceutical composition of claim 16, wherein the caffeic acid amide compound has the chemical structure of:

25. The pharmaceutical composition of claim 16, wherein the caffeic acid amide compound has the chemical structure of:

26. A method for treating proliferative skin disorders, comprising:

applying a topical pharmaceutical composition to a lesion, wherein the topical pharmaceutical composition comprises a caffeic acid ester compound having the chemical structure of;

and the topical pharmaceutical composition comprises the caffeic acid ester compound at a concentration by weight within a range from about 0.01% to about 20%.